Kidney Week

Abstract: SA-PO155

Hydrogen Sulfide Alleviates Cisplatin-Induced AKI by Targeting Pyroptosis

Session Information

• AKI: Metabolism and Cell Death
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Han, Zhenyuan, Department of Nephrology, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China

Zhenyuan Han

• Jia, Yutao, Department of Nephrology, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China

Yutao Jia

• Deng, Tianyu, Department of Nephrology, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China

Tianyu Deng, MS

• Ren, Zhiyun, Department of Nephrology, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China

Zhiyun Ren, PhD

• Wang, Weiwan, Department of Nephrology, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China

Weiwan Wang

• Wang, Xiaoyan, Department of Nephrology, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China

Xiaoyan Wang, MD, PhD

Background

Our previous studies have demonstrated that GYY4137, a long-acting hydrogen sulfide(H₂S) donor, exerts a remarkable protective effect on diabetic renal damage by affecting multiple ROS-associated enzymes. According to animal experimental research reports, exogenous H₂S donors alleviate the renal toxicity caused by cisplatin, mainly through anti-inflammatory, antioxidant, autophagy, etc. However, the effect of H₂S on pyroptosis in cisplatin-induced AKI(cis-AKI) is currently unclear.

Methods

Male C57BL/6J mice (7-8 weeks old), were randomly divided into 3 groups (n=7/group). Cisplatin (20 mg/kg) was given by a single intraperitoneal injection to both cisplatin group and cisplatin+GYY group, the latter was given GYY4137(100mg/kg) by daily intraperitoneal injection for 4 times, a day before cisplatin. The control mice were given 0.9% saline. Blood and kidney samples were collected after the mice were sacrificed on day 3 of cisplatin. Data was shown as mean±SE, while significance(P<0.05) was achieved by one-way ANOVA, and Holm-Sidak posthoc test.

Results

Compared to the control group, cis-mice showed an increase in serum creatinine (82.22±6.05 vs 57.3±2.4, umol/L) and urea nitrogen (23.3±1.1 vs 6.5±0.3, mmol/L). Histological analysis also revealed severe damage to the renal cortex, characterized by vacuole-like degeneration of tubular epithelial cells, loss of brush border, and tubular cell necrosis. There were increases of NLRP3 (121.9±5.2) and GSDMD (127.3±1.7) in cis-group, indicating an activation of classical pyroptosis. In the non-classical pyroptosis pathway, caspase3 (132.9±2.1) and GSDME (209.1±8.2) were significantly elevated in response to cisplatin treatment. Treatment with GYY4137 mitigated serum creatinine levels (63.6±4.6) and blood urea nitrogen (18.1±1.7) and reduced histological damage to the renal cortex in cis-mice. Moreover, it normalized or reduced the cis-mediated increases in pyroptosis-related proteins, including caspase3 (106.9±5.9), GSDME (173.8±11.2), NLRP3 (88.3±4.3), and GSDMD (97.1±6.4).

Conclusion

Exogenous hydrogen sulfide may alleviate cis-AKI via inhibiting caspase3-dependent or independent pyroptosis.

Funding

• Government Support – Non-U.S.